chr16-55502815-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004530.6(MMP2):c.1806C>T(p.Phe602Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,612,436 control chromosomes in the GnomAD database, including 151,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11173 hom., cov: 32)

Exomes 𝑓: 0.43 ( 140039 hom. )

Consequence

MMP2
NM_004530.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.952

Publications

36 publications found

Variant links:

Genes affected

MMP2 (HGNC:7166): (matrix metallopeptidase 2) This gene is a member of the matrix metalloproteinase (MMP) gene family, that are zinc-dependent enzymes capable of cleaving components of the extracellular matrix and molecules involved in signal transduction. The protein encoded by this gene is a gelatinase A, type IV collagenase, that contains three fibronectin type II repeats in its catalytic site that allow binding of denatured type IV and V collagen and elastin. Unlike most MMP family members, activation of this protein can occur on the cell membrane. This enzyme can be activated extracellularly by proteases, or, intracellulary by its S-glutathiolation with no requirement for proteolytical removal of the pro-domain. This protein is thought to be involved in multiple pathways including roles in the nervous system, endometrial menstrual breakdown, regulation of vascularization, and metastasis. Mutations in this gene have been associated with Winchester syndrome and Nodulosis-Arthropathy-Osteolysis (NAO) syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

MMP2 Gene-Disease associations (from GenCC):

multicentric osteolysis, nodulosis, and arthropathy
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
multicentric osteolysis-nodulosis-arthropathy spectrum
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MMP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 16-55502815-C-T is Benign according to our data. Variant chr16-55502815-C-T is described in ClinVar as Benign. ClinVar VariationId is 319768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.952 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP2	NM_004530.6 link	c.1806C>T	p.Phe602Phe	synonymous_variant	Exon 12 of 13	ENST00000219070.9	NP_004521.1	P08253-1A0A024R6R4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000219070.9 link	c.1806C>T	p.Phe602Phe	synonymous_variant	Exon 12 of 13	1	NM_004530.6	ENSP00000219070.4		P08253-1

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55716

AN:

151980

Hom.:

11168

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.652

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.405

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.394

GnomAD2 exomes

AF:

0.398

AC:

99911

AN:

251262

AF XY:

0.402

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.419

Gnomad ASJ exome

AF:

0.393

Gnomad EAS exome

AF:

0.241

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.457

Gnomad OTH exome

AF:

0.420

GnomAD4 exome

AF:

0.433

AC:

633002

AN:

1460338

Hom.:

140039

Cov.:

AF XY:

0.432

AC XY:

313973

AN XY:

726546

show subpopulations

African (AFR)

AF:

0.183

AC:

6119

AN:

33466

American (AMR)

AF:

0.419

AC:

18752

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

10237

AN:

26130

East Asian (EAS)

AF:

0.260

AC:

10306

AN:

39688

South Asian (SAS)

AF:

0.358

AC:

30840

AN:

86226

European-Finnish (FIN)

AF:

0.402

AC:

21433

AN:

53342

Middle Eastern (MID)

AF:

0.407

AC:

2336

AN:

5734

European-Non Finnish (NFE)

AF:

0.457

AC:

508000

AN:

1110694

Other (OTH)

AF:

0.414

AC:

24979

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

18443

36887

55330

73774

92217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14972

29944

44916

59888

74860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.366

AC:

55738

AN:

152098

Hom.:

11173

Cov.:

AF XY:

0.363

AC XY:

26983

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.191

AC:

7937

AN:

41512

American (AMR)

AF:

0.441

AC:

6737

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

1401

AN:

3462

East Asian (EAS)

AF:

0.242

AC:

1247

AN:

5144

South Asian (SAS)

AF:

0.336

AC:

1618

AN:

4822

European-Finnish (FIN)

AF:

0.399

AC:

4222

AN:

10576

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.457

AC:

31045

AN:

67974

Other (OTH)

AF:

0.390

AC:

823

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1752

3503

5255

7006

8758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

540

1080

1620

2160

2700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.417

Hom.:

11519

Bravo

AF:

0.362

Asia WGS

AF:

0.248

AC:

861

AN:

3478

EpiCase

AF:

0.453

EpiControl

AF:

0.449

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Multicentric osteolysis nodulosis arthropathy spectrum

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

8.7

(source)

DANN

Benign

0.89

PhyloP100

0.95

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over